Mendus AB (publ) (IMMU) Earnings Call Transcript & Summary

Good morning, everyone. I'm Erik Manting. Today I'm joined by Jeroen Rovers, Chief Medical Officer of Mendus; and Lotta Ferm. We look forward to providing an update on the year until now, including the third quarter, following the publication of our third quarter report, and then have it followed by Q&A by the analysts that are following us. This afternoon, we will also have a lunch at our headquarters. So we look forward to also communicating with investors at that event. We are public listed company. Our disclaimer, of course, can be found on our website also. Let us start with a brief summary of what Mendus is about. We are pioneering cancer maintenance therapy. Cancer maintenance therapy means that we treat cancers after they have undergone first treatment, very often chemotherapy with -- where the risk of recurrence is very high. We have an ongoing Phase II trial in acute myeloid leukemia, which is a cancer that recurs very quickly, if untreated. And the same thing for ovarian cancer, where we have a Phase I trial, and we have additional programs in solid tumors with intratumoral primer called ilixadencel cell and a preclinical NK cell program. The progress in 2023 has been mainly focused on the data that we presented end of last year at ASH, which is the American Society of Hematology, largest conference in the world. We had a plenary session because we believe we had breakthrough data in the AML cancer maintenance setting. And that was the basis for us to focus on the program by looking into additional data from the trial. We have collected so-called immunomonitoring data, which means we look into the immune responses of patients following the vididence treatment. We published those data at renowned conference such as the European Hematology Association Meeting and, Immunotherapy Conference CICON in Milan. Also very importantly, we were able to secure additional financing in -- which we completed in July of this year, and we have set up a manufacturing alliance with NorthX Biologics based here in Sweden. The reason for the manufacturing alliance is that we need to step up our manufacturing towards large scale to facilitate for latest clinical development and in the end commercialization, and it takes time. So we have developed a process but to implement it in a so-called GMP or clinical or commercial manufacturing setting. It's a big effort, which we will do together with Northx so they have become an important alliance and an important partner for the company. We also secured in the third quarter Fast Track designation by the U.S. FDA for vididencel in AML. It means we can go back to the regulator, more often with questions. And also, we have a chance of potential faster approval route at the end of the development of the product. So it's a very valuable, additional regulatory validation for the program. We have a Phase I study completed already some years ago and published that we did a lot of extra work on that trial and the data are actually quite relevant also for the way forward for vididencel. We have published that paper about a week ago in Journal called HemaSphere, which is the official journal of the European Hematology Association, and the data has showed effect both in high-risk MDS patients and AML patients, which also gave us a nice insight in the mutation of the tumors that the patients were having that gives a certain risk profile. And we saw also patients with high-risk humans responding to our therapy. And that's a very encouraging signal. And finally, we also looked in the Phase I trial into the combination with azacitidine, and that was a combination that worked out quite nicely and which is an important validator also for the path forward for combining the 2 drugs in the future. Finally, we had an update on the ovarian cancer trial, the ALISON trial, most recently at the Society of Immunotherapy Conference, which shows that the product also triggers in ovarian cancer patients, very strong and robust immunity. Then we have, of course, the other programs, we published preclinical work around ilixadencel in combination with specific checkpoint inhibitors, and we have in preparation a trial with ilixadencel in soft tissue sarcoma. So it was all in all, I think a very successful and very busy year, and this is the summary of everything we did until the publication of the report this morning. As a summary of our pipeline, we will focus on the top part, which is the vididencel program in AML, which is the most advanced program, and that will be in 2 ways. First of all, explaining the basic principle and then looking more into the data. First of all, the principle is that we try to prevent tumor recurrence. Tumor recurrence is actually the largest cost of tumor-related deaths in the treatment of cancer. So it's not the initial tumor that is deadly, but it's the recurrence. What we try to do is to prolong disease-free survival and so delay the recurrence of the disease. That's a very important starting point for our unique positioning in the cancer therapy landscape. We do that with products we believe that has a very competitive product profile because, first of all, it's biology, we understand very well. It's biology to make cancer cells highly immunogenic by forcing them to adopt dendritic cell phenotype and thereby, they become a very strong initiator of new responses against a broad array of tumor-associated antigens. And that's a very potent vaccine. What's also very important as a company is that you know how to manufacture your products. So we have developed not only proprietary cell line and of course, also the cell banks that come with it, which are all proprietary to the company. But also, we have developed our own manufacturing process, which is also validated, for example, by an ATMP certificate by the EMA. The product is straightforward in its use. It's stored as a frozen product, and it can be shipped to the hospitals on demand and is administered via simple intradermal injection. It triggers strong immune responses, both in vitro and in vivo, but now also we have a well-documented mechanism of action, but also we see in the clinical trial so far, very robust boosting of immune responses. That balances with very mild product-related side effects. But the only side effect we've currently observed related to the products is actually injection site reactions, where, of course, the product triggers local information. Finally, we have strong regulatory validation of the product in the form of an orphan drug designation, both in the U.S. and Europe and the recently acquired Fast Track Designation for the product. One important element to highlight about maintenance therapy is that it should, of course, result in durable responses, meaning longer-term relapse-free and overall survival benefit. But also, it should not come at the cost of a high burden to the patient's health because patients have already undergone high-dose chemotherapy and have already a pretty weak physical state. So they need to recover. So with the maintenance therapy, you can't have a very toxic side effect profile. Our product has a very safe side effect profile. So that makes it also competitive in the AML maintenance setting. This is the current only approved drug in AML maintenance. It's called oral azacitidine. And what you see here on the top is overall survival curves. And on the bottom, relapse-free survival curves. And what's immediately clear is that there is little difference between overall and relapse-free survival and also that there is relatively little difference between untreated patients, which are the blue lines and the treated patients, which are the red lines. So it means that the azacitidine slows down the disease but in the end, all patients relapse. And that's particularly the case for the patient population on the right, which have so-called measurable residual disease. So already remaining cancer cells that you can pick up by sensitive methods in the blood. Those patients have the highest risk of recurrence, and that is the patient population we included in our Phase II monotherapy trial. So all the patients that were enrolled in the ADVANCE II trial were MRD-positive at start. And this is the result we published end of last year and which we have, of course, presented before, but the relevance of this is hard to overstate. The relevance of this is that the majority of patients was not only alive at the end of the study period, which was 70 weeks, but also remained alive in disease-free in the long-term follow-up now between 16 and 48 months. This is data that we continue to collect, and we will present also again as an oral presentation at ASH this year. So an update of this trial will be presented on December 11 at ASH. What's also important is the underlying science that we do to measure both the disease response and the immune response. And this is a very basic summary of showing that the strength of the immune response also correlates very nicely with the clinical effect that we see. And this is a very important part of the trial because it validates the approach and it supports the mode of action of our product. What we have done in the broader AML field is to first focus on the trial in combination with oral azacitidine. We will announce the details of the trial before the year-end, and we also hope that the trial will start immediately, we will explain what the trial will look like, but the most important element to realize now is that it focuses on the combination with oral azacitidine, but that there's also a lot of other opportunities to explore AML maintenance setting in other patient populations. For example, following bone marrow transplant or HSCT or following patients that have been treated with another chemotherapy, which is azacitidine plus Venetoclax. The first, we will focus on the trial in combination with current standard of care being oral aza, but again, with the possibility to later on broaden the positioning in the AML maintenance landscape. This is what the trial strategy looks like. So we are currently on the top in the monotherapy trial. We will have a next readout in December of this year. And then, of course, we will also go back to the FDA for an end of Phase II meeting after we have concluded most of the collection of the trial data. And in the meantime, we are already preparing for the trial in combination with oral azacitidine. This is a trial that will comprise of 2 parts. Again, we will disclose the details once we have basically concluded all the preparatory work. But the most important part is we start with a trial with 2 arms, control arm with vididencel -- sorry, control arm with azacitidine only versus a treatment arm with azacitidine and vididencel, but we have the possibility to scale up that trial to larger patient numbers. In parallel, we will start to prepare for a global registration trial. And for that, we will collect the data from the monotherapy trial, but also the initial data from the Phase II trial in combination with oral azacitidine. As an important underlying pillar also is the manufacturing alliance we have in place with NorthX. And what we need to do in parallel to preparing for pivotal stage development and in the end commercialization is also make sure that our manufacturing keeps pace with the late-stage development and in the end, also market registration. That takes time. That's why we are very happy we have started the collaboration with NorthX in the third quarter to scale up the manufacturing of vididencel. What is nice is that there's multiple synergies. We have, of course, Mendus developed the process and the underlying dendritic cell biology and all the know-how we have on the regulatory front about our product, NorthX has the GMP, know-how, and licenses, but also the actual facilities or the factory where we will make the product and that is coming together now in the start of the alliance that we initiated in the third quarter. To finish it up, the positive monotherapy data with vididencel support the development of the product as an AML maintenance treatment. The next data of the ADVANCE II trial will be presented at ASH in December of this year, on December 11 to be precise as an oral presentation by the principal investigator. We have a clear clinical development plan. We will start with the combination trial with oral azacitidine, and that's a step-up towards pivotal stage development. Then we have the possibility to expand the indication in the broader AML maintenance setting, and we have a manufacturing alliance with NorthX Biologics to support large-scale manufacturing. Additional readouts from the ongoing vididencel Phase I trial in ovarian cancer, will take place in the first half of '24. And finally, we are preparing for ilixadencel to be entering a trial in soft-tissue sarcoma in 2024. With that, I thank you for your attention, and we open the line for Q&A with the analysts that are dialing in. Thank you.

[Operator Instructions] the next question comes from Chien-Hsun Lee from Pareto.

So yes, maybe I'll start with the first question. So in your ovarian cancer study, you mentioned that vididencel chose the potential to boost the broad immune response. Do you also see it in the AML trial? And if so, how does it create between the 2 trials?

Chien, thanks so much for your question. I will pass this one on to Jeroen, the Chief Medical.

That's a great question. I think what we do, not only in the ALISON study, but we also did that already in the ADVANCE II study and also in the first Phase I study is we clearly try to evaluate whether injecting vididencel leads to an immune response against, say, the antigens, which we basically bring into the patient. And that we do by doing assays where you really are measuring specific T cell responses against these intracellular antigens, which we know are carried by the origin of the cell. So that's a leukemic cells, so that's a cancer cell. In the ADVANCE II, we've tested a range, meaning at least 3 different antigens, the most predominant for AML. That's WT-1, that's PRAME, that's RHAMM. But there's a limitation to the amount of material you have available for testing a much wider range. But in the ADVANCE II study, we clearly saw that it didn't really matter which antigen. We saw responses against all of these 3 antigens, not all at the same time in all patients, but we saw them happening both to WT-1, PRAME and RHAMM. And what -- for us was a positive surprise in ADVANCE II study was we saw in heavily treated patients with, in this case, AML that 17 out of the 20 showed at least 1 T cell response. So that's something which a lot of people in advance of this study warned us like, you probably cannot see so much response in a heavily-pretreated patient population. Well, the answer is we do. And so that's a very positive signal. And the same magnitude of cell responses, we now see in a different indication like what you just indicated in the ovarian cancer patients. There, what we released on Monday at SITC, it was that in 6 out of the 8 patients we tested, and it's an ongoing study. So we're still testing the additional patients, which are being treated. So we will get more data. But it's 6 out of the 8, we saw that there was a similar, say, pattern that we saw vaccine-induced responses. Now one of the additional things we did in the ALISON study is that next to testing the intracellular antigens, which we know is carried by our product, we also tested some antigens, which we know can be relevant for cancer. And we saw that those antigens also that we saw T cell responses against those antigens. And that's the remark made that we see a broader response, and you call that like epitope spreading. And that's due to the fact that there is a response, so there's an effect of the treatment on to the tumor, tumor cells. And they then, of course, when they die, release their antigens. So you get a response to those as well. And I think that's the additional broadening of the response, which we can clearly see in the ALISON study, but we saw that in the Phase I AML study as well.

Okay. I see it. Yes, I think those are very good points. And maybe a follow-up question. So for your upcoming combo trials with oral aza, could you provide on the time line? And so what kind of patient number, could you provide a range that you're thinking about?

Yes. So what Erik just also indicated, of course, our next step for development of vididencel in acute myeloid leukemia is to start a Phase II study where we combine the vididencel with the current standard of care being the oral formulation of azacitidine. The study we're going to set up is a randomized clinical trial. I think that's the importance of this study as well because now we're going to show whether it's vididencel in combination with azacitidine is first safe but secondly, effective over, say, only using oral azacitidine. And we're close to finalizing say, the agreement with a large collaborative research group, and that's to be announced soon. And that will be a study which will then start to run and hopefully randomize 40 patients initially to test the safety of the combination with the potential to expand that study to a larger group of patients.

The next question comes from Christian Binder from Redeye.

Just one from my side. Regarding the upcoming Phase II trial in case you choose to expand the trial and then also regarding the Fast Track designation that you received recently and all the other designations. If results are similarly positive as an ADVANCE II, would you expect that there is a chance for, for example, accelerated approval? Or there any other ways in which you think you recently obtained Fast Track designation can help you bring vididencel to market faster.

Yes. Maybe starting with the overall strategy and then handing it over to Jeroen for the more specific regulatory aspects, Christian. I think what we are doing, and maybe we should do it more explicitly is we are building up a network of clinical trials that we want to work with. That's also an important part of preparing for pivotal stage development. The ongoing trial has allowed us to build up a broader network throughout Europe. As you know, we are running the trial with 10 clinical centers in the Netherlands, Germany, the Scandinavian countries, including Sweden, but the global registration trial that we are planning for, of course, will require additional networks also in other parts of the world. And that is why we are stepwise also expanding that network. And that will be part of the strategy of the company, including also the next trial with oral azacitidine. With respect to potential approval of the product and potential accelerated approval to the product, that will, of course, depend on the interactions with the regulators. But maybe Jeroen, you can say a bit more about this, what we expect there.

Yes. I think a very short answer is, of course, if we have, say, outstanding results, then we will definitely go for trying to get a say, faster part to market. I think that's something which, yes, will be helped by also the fast-track designation because that allows us to have, say, a more easier and for more frequent interaction in this case, specifically, of course, with the U.S. regulators, with the FDA but also within Europe, we're constantly interacting with the authorities to see how we can bring these products to effect. The expansion of the study, we're now going to embark it will, of course, not happen, say, next year. So we need to time too, to enroll these 40 patients. And on the basis of that, we know whether we can actually expand it. But if the results are from the efficacy point of view, stellar enough for sure, we will use those for the further interactions with the authorities.

The next question comes from Soo Romanoff from Edison Group.

Helpful. And a lot of the questions that were asked were helpful as well. The data from the ASH abstract show that the majority of the patients had favorable [ ELN 2017 ] risk score. In your experience, how important is that predictor for relapse?

Yes. Thank you, Soo, for the question. I think in general, of course, yes, the risk score is there for a reason. So the risk of maybe getting relapsed is higher with patients with an advanced risk score versus the one with the favorable risks score. But having said that, of course, that's based on, say, data from, say, chemotherapy treatments in the past. Whether that holds up for, say, immunotherapy still has to be seen. But if you look at the data, as we published it in the abstract, yes, the majority is based on ELN 2017 favorable risk, meaning 13 patients were favorable. But if you use the score, which was used, for instance, for the registration trial of oral azacitidine, that was a difference core. They didn't use ELN 2017. They used an earlier risk store than if we apply that to our patients, then we have the majority of patients being of an intermediate risk. We looked at it, whether there is a big impact on the risk score throughout this study, but the numbers are small. And thus far, we didn't see any major, say, differences in that respect.

I think, Soo, just to add to that and also for the general audience, AML is very high-risk disease, independent of the risk score, it remains high-risk disease. And certainly, MRD-positive status is an imminent sign of relapse being also very short after, let's say, MRD positive status. So that's one part. The other part, which Jeroen alluded to is chemical drugs tried to slow down the growth of cancer cells. And that is something which also, to a large extent, determines the risk scoring of patients and how that plays out in the clinic. What we start to see, and again, being careful because patient numbers are still low but it is actually with immunotherapy, you have a very different outcome. And that's also part of the paper we published around the Phase I data. One of the reasons we did go back to the Phase I data and did a lot more analysis on the patients. Also patients with a very poor prognosis based on their risk score responded well to the immunotherapy treatment. So these are all signs that the way a chemical drug works and slowing down the growth of cancer cells may be very different from the way an immunotherapy works that basically boost the immune system back on controlling residual cancer cells. We have to provide a bit more context to the answer. Any other questions from you, Soo?

No, I think that's good.

The next question comes from [ Andy Siltanen ] from [indiscernible].

I have 3 questions for you. So firstly, you previously reported on immunological differences in AML patients who are very dense responders versus nonresponders. So I wonder if you can comment a little bit on the prospects of using biomarkers and patient selections when you are going to future trials.

So I'll give an initial conceptual answer, Andy, and then I'll ask Jeroen to go into a bit more depth in response to your question. The simple question is, of course, can you predict whether the patients will respond to the therapy or not? And that's currently not the case. The only thing we see is that patients that are not responding, generally have a very poor immune system. And that relates to the nature of the disease, it relates to the chemotherapy. So basically, not all immune systems are fit enough anymore to respond to immunotherapy. But of course, the important outcome of the ADVANCE II trial is that the majority of patients actually did show a pretty robust and new response and the product is relatively safe, which means that it has a very good risk-benefit profile. So therefore, we are currently not planning to exclude patients based on specific criteria for future trials. But of course, it is an important confirmation of the mode of action of the therapy, but we do see these differences between responders and nonresponders. Jeroen, you want you add?

No, I think that covers it. I think it's clear here that, we look at it to learn. But at the moment, it's not a predictor in our view. And like what Erik said, it is, of course, common that a certain patient might have a different, say, immune status at the start of any treatment. And I think what comforts us is that what I indicated earlier. Even if we look at heavily pretreated patients like these AML patients in the ADVANCE II study, that out of these 20 patients, we saw 17 to at least have 1 immune response to these antigens, which are carried by our product. That is, in my view, a very high percentage in this pretreated patient population. And but we continue to monitor, of course. And if in the future, might leads to clear, say, biomarkers, we for sure will use it.

So my second question is on production. So you talked about ramping up vididencel production. So can you comment at all on the level of investment that we can expect going forward?

Yes, to a certain extent, Andy. I think you always have to make sure that your manufacturing keeps the same pace as your clinical development, right? So in the background, we have always been working in-house on the further optimization of our manufacturing processes and also the improvement, of course, of the regulatory dossier around the product. But in the end, you need manufacturing infrastructure, which means a factory where you can make a product. We are currently working with the manufacturer in Germany that has already manufactured already the material we need for the upcoming trials. But in the end, if you want to go to a Phase III trial, in the end market registration, you have to have a much larger infrastructure. And that is what we were able to establish with NorthX. And the deal we have with NorthX is to help us until at least the end of '25 to make sure that we will have all the material we need for that larger registration trial we are preparing for. So that is the first very big step in making sure we are ready for it. In the end, of course, when you go to a global market, you may even envision making product also in other parts of the world. But the nature of the product doesn't require it because we make it in bulk, we freeze it, and we can ship it. So for now, I think this is the main step we need to take to realize the 2 main goals, which is a registration trial, and the end market approval.

And then my final question is kind of a higher level question. So in vaccination in general, younger people tend to develop a stronger immune response. So what are your thoughts on your vaccination approach? So are you -- do you expect it to work better for younger subjects versus elderly patients?

Jeroen, you want to answer that?

Yes. I think I did. It almost comes back to the first question. So as we know, of course, that one of the reasons why for general vaccination strategies and the younger patients tend to have a say, maybe a better response sometimes, it probably has to do with the state of the immune system. And the fact that when you become older, your immune system might be a bit less responsive, doesn't exclude that you can still manage the response. I think it's then a matter of priming the system well enough. So if you frequently enough, say, expose also an older immune system to these antigens, which -- where you want to trigger a response through, then it also works. So yes, there is, by nature, I think, this link between any say, active immunotherapy in this case, a vaccination and potential age, but that is more the link to the state of the immune system as what we indicated in the first question. And so yes, if you are having an immune system, which is not responding that well, you might respond to not immediately to an active vaccination approach. And that could well have to do with you being older, yes.

So operator, are there any more questions? Or does this conclude the webcast.

There are no more questions at this time. So I hand the conference back to the speakers for any closing comments.

Well, first of all, thank you all for joining this webcast about the update of Mendus until today. And of course, we're looking forward to a strong ending of the year. We will conclude this webcast now, but we will have an investor lunch later today, and we look forward to seeing our investors there and potentially also some of you who have joined the webcast. Thanks so much.